Winter 2015

Memphis, Tennessee

Multidisciplinary clinic cares for children with kidney, urinary tract anomalies

Le Bonheur Children’s Nephrologist David

Hains, MD, formed a monthly CAKUT

(Congenital Anomalies of the Kidney and

Urinary Tract) clinic in June. The clinic brings

specialists from nephrology and urology together in

one setting to care for children with chronic kidney

disease, recurrent urinary tract infections (UTI) and

other anomalies.

“Children with congenital anomalies of the

kidney and urinary tract present unique and com-

plex medical issues that require a multidisciplinary

approach,” said Hains. “By having a team of subspe-

cialists all see a patient and their family in one visit,

a collective plan can be discussed amongst the

family and medical team and implemented.”

Hains is director of Le Bonheur’s Innate

Immunity Translational Research Center. His lab has

received National Institutes of Health funding to

determine how genetic factors play a role in recur-

rent UTIs in children with vesicoureteral reflux.

Bissler recognized for TSC workJohn Bissler, MD, chief

of Pediatric Nephrology at Le Bonheur, recently received Tuberous Sclerosis Complex International’s research award for his work with Chinese patients with tuberous sclerosis com-plex (TSC). Bissler received the award at the 2014 International Research Conference on TSC/LAM in Beijing.

Bissler also received 2014 Manual R. Gomez award from the TS Alliance for his extraordinary scientific and humanitarian efforts to find a cure for TSC, while improv-ing the lives of those affected.

Bissler is co-leader of the hospital’s TSC Center of Excellence, which treats TSC patients and conducts research.

RIVUR study: Antibiotics reduce UTIs for kids with reflux

Le Bonheur’s Chesney co-authors NEJM study

A study published in May’s New England Journal of Medicine showed that long-term antimicro-bial prophalaxis can significantly reduce the risk of recurrent uri-nary tract infection in children with vesicoureteral reflux. The findings are part of the national RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial.

The study – funded by the National Institutes of Health – was co-authored by Le Bonheur Children’s Nephrologist Russell Chesney, MD, who serves as chairman of the RIVUR study steering committee.

“We hope these findings will help inform physicians – and parents – on the best ways to treat children with reflux who develop urinary tract infections, depending on their grade of reflux,” said Chesney. “We also think this may lead to more debate about the need for imaging studies in children with reflux.”

Research uses novel models to find prevention therapies for TSC-associated renal disease

Nephrology Chief John Bissler, MD, recently received funding from the United States Department of Defense to identify therapies to prevent tuberous sclerosis complex (TSC)-related renal disease. His research will use novel models that phenocopy human renal disease.

The new models are the next step in Bissler’s research, after he published a study this year citing evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy.

Atherton brings additional expertise to team

Pediatric Nephrologist Jim Atherton, MD, MS, has joined Le Bonheur’s Nephrology team. Atherton completed residency and fellowship training at Le Bonheur and the University of Tennessee Health Science Center.

Atherton also recently received a master’s degree in biomedical engineering from the University of Memphis – training that will add much value to the Nephrology team.

John Bissler, MD

Nephrology Update

Russell Chesney, MDJim Atherton, MD, MS

Hains’ Innate Immunity Translational Research Center has received National Institutes of Health funding to determine how genetic factors

play a role in recurrent UTIs in children with vesicoureteral reflux.2014-15NEPHROLOGY

HOSPITALSCHILDREN’SBEST

Non-Profit Org.

US POSTAGEPAID

Memphis, TNPermit No. 3093

848 Adams Avenue

Memphis Tennessee 38103

Nephrology Update is a publication of Le Bonheur Children’s Hospital.

John Bissler, MD Chief

Jim Atherton, MD Bettina Ault, MD Russell Chesney, MD Noel Delos Santos, MD David Hains, MD Margaret Colleen Hastings, MD Robert Wyatt, MD

/ lebonheurchildrens@LeBonheurChild /lebonheurchildrens

About Le Bonheur Children’s Hospital

• 255-bed free-standing children’s hospital in Memphis, Tenn.• Ranked as a best children’s hospital by U.S. News & World Report• Designated Level 1 pediatric trauma center by the American College of Surgeons• Pediatric partner of the University of Tennessee Health Science Center and St. Jude Children’s Research Hospital• 24-suite FedExFamilyHouse provides housing for families who travel long distances to Memphis

Publications and Presentations: 2014

PublicationsHoberman A, Greenfield S, Mattoo T, Keren R, Mathew R, Pohl H, Kropp B, Koogs S, Nelson C, Moxey-Mims M, Chesney RW, Carpenter M.: Antimicrobial prophylaxis for children with vesico-ureteral reflux. New England Journal of Medicine, 370(25)2367-2376, 2014.

Wassner SJ, Chesney RW, Friedman A, Chantler C, Portale AA. Malcolm A. Holliday, M.D, January 12, 1924 - March 26, 2014. Pediatr Nephrol Aug;29(8):1473-4. doi: 10.1007/s00467-014-2833-4. Epub 2014 May 11. No abstract available. PMID:24817341

Chesney RW1, Chevalier R. Thirty-three years of progress: the International Workshops on Developmental Nephrology and the role of IPNA. Pediatr Nephrol. 2014 Apr;29(4):499-504. doi: 10.1007/s00467-013-2750-y. Epub 2014 Jan 23

Chesney RW, Dabbagh S, Han X: Newer Insights into the Taurinuria of Vitamin D-Deficiency. 19th International Taurine Meeting, Krakow, Poland, 2014 (In press, Taurine 9).

Han X, Patters AB, Ito T, Azuma J, Schaffer SW, Chesney RW: Knockout of the TauT gene predisposes C57BL/6 mice to STZ-induced diabetic nephropathy. 19th International Taurine Meeting, Krakow, Poland, 2014 (In Press, Taurine 9).

Chesney RW, Dabbagh S, Han X: Newer Insights into the Taurinuria of Vitamin D-Deficiency. 19th International Taurine Meeting, Krakow, Poland, 2014 (In press, Taurine 9).

Mattoo TK, Chesney RW, Carpenter MA, Moxey-Mims, M, For the RIVUR Investigators. The RIVUR Study: A Factual Interpetation of out data. Pediatric Nephrology

Alford El, Chimm RF, Crill CM, Hastings MC, Ault BH, Shelton. CM Glomerular Filtration Rate Equations Do Not Accutagely Predict Vancomycin Trough Concentrations in Pediatric Patients. Ann Pharmacother. 48 (6):691-6, 2014. PMID: 2464680.

Skandarajah A, Hains DS and Schwaderer AL. “UTI, Familial Occurrence and Association with other infections.” Journal of Clinical Pediatric Nephrology. 2014 Vol 2: 1.

Shin HS, Becknell B, Reagan P, Mahan JD, Hains DS. “Modern U.S.A. Trends in Demographics, Extrarenal Manifestations, and Inpatient Healthcare Utilization for Hemolytic Uremic Syndrome.” Accepted to Journal of Clinical Pediatric Nephrology on April 2, 2014.

Becknell B, Eichler T, Beceiro S, Li B, Easterling R, Carpenter AR, Partida-Sanchez S, Hains DS, Spencer JD. “Ribonuclease 6 and Ribonuclease 7 Expression and Antimicrobial Function in the Human and Murine Urinary Tract.” Kidney Int. 2014 Jul 30. doi: 10.1038/ki.2014.268. [Epub ahead of print] PubMed PMID: 25075772.

Hains DS, Chen X, Saxena V, Barr-Beare E, Flemming W, Easterling R, Becknell B, Schwartz GJ, Schwaderer AL. Carbonic anhydrase 2 deficiency leads to increased pyelo-nephritis susceptibility. Am J Physiol Renal Physiol. 2014 Aug 20. pii: ajprenal.00344.2014. [Epub ahead of print] PubMed PMID: 25143453.

Schnaper HW, Schubert K, Perlman SA, Clark SL, Hains DS, Roach JL, Skversky AL, Spencer JD, Springel T, Swartz  SJ, Norwood VF and Satlin LM. Training the next generation of pediatric nephrology advocates: the John E. Lewy Foundation Advocacy Scholars Program.  J Pediatr, in press.

Hastings MC, Chesney RW. What is “masked syndrome of inappropriate intidiuretic hormone?” Is it an “isonatremic syndrome(letter) J. Pediatr. Accepted for publication.

Alford El, Chimm RF, Crill CM, Hastings MC, Ault BH, Shelton. CM Glomerular Filtration Rate Equations Do Not Accutagely Predict Vancomycin Trough Concentrations in Pediatric Patients. Ann Pharmacother. 48 (6):691-6, 2014. PMID: 2464680.

Suzuki H, Raska M, Yamada K, Moldoveanu Z, Julian BA, Wyatt RJ, Tomino Y, Gharavi AG, Novak J: Cytokines alter IgA1 O-Glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes. Journal of Biological Chemistry 289: 5330- 5339, 2014.

Kiryluk, K; Y; Scolari, F; Sanna-Cherchi, S; Choi, M; Verbitsky, M; Fasel, D; Lata, S; Prakash, S; Shapiro, S; Fischman, C; Snyder, HJ; Appel, G; Izzi, C; Viola, BF; Dallera, N; Del Vecchio, L; Barlassina, C; Salvi, E; Bertinetto, FE; Amoroso, A; Savoldi, S; Rocchietti, M; Amore, A; Peruzzi, L; Coppo, R; Salvadori, M; Ravani, P; Magistroni, R; Ghiggeri, GM; Caridi, G; Bodria, M; Lugani, F; Allegri, L; Delsante, M; Maiorana, M; Magnano, A; Frasca, G; Boer, E; Boscutti, G; Ponticelli, C; Mignani, R; Marcantoni, C; Di Landro, D; Santoro, D; Pani, A; Polci, R; Feriozzi, S; Chicca, S; Galliani, M; Gigante, M; Gesualdo, L; Zamboli, P; Battaglia, GG; Garozzo, M; Maixnerová, D; Tesar, V; Eitner, F; Rauen, T; Floege, J; Kovacs, T; Nagy, J; Mucha, K; Pączek, L; Zaniew, M; Mizerska-Wasiak, M; Roszkowska-Blaim, M; Pawlaczyk, K; Gale, D; Barratt, J; Thibaudin, L; Berthoux, F; Canaud, G; Boland, A; Metzger, M; Panzer, U; Suzuki, H; Goto, S; Narita, I; Caliskan, Y; Xie, J; Hou, P; Chen, N; Zhang, H; Wyatt, RJ; Novak, J; Julian, BA; Feehally, J; Stengel, B; Cusi, D; Lifton, RP; Gharavi, AG. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intes-tinal pathogens. Nat. Genet., 2014 vol. 46(11) pp. 1187-96.

Guay-Woodford, L.M., Bissler, J.J., Braun, M.C., Bockenhauer, D., Cadnapaphornchai, M.A., Dell, K.M., Kerecuk, L., Liebau, M.C., Alonso-Peclet, M.H., Shneider, B., Emre, S., Heller, T., Kamath, B.M., Murray K.F., Moise, K., Eichenwald, E.E., Evans, J., Keller,. R.L., Wilkins-Haug, L., Bergmann, C., Gunay-Aygun, M., Hooper, S.R., Hardy, K.K., Hartung, E.A., Streisand, R., Perrone, R., and Moxey-Mims, M. (2014) Consensus expert recommendations for diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J. Pediatr 165, 611-617.

Siroky, B. J, Yin, H., Dixon, B.P., Reichert, R.J., Hellmann, A.R., Ramkumar, T., Tsuchihashi, Z., Bunni, M., Dillon, J., Bell, P.D., Sampson, J.R., and Bissler, J.J. Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy. 2014 Am. J. Physiol. Renal Physiol. 307, F560-570.

Kingswood, J.C., Jozwiak, S., Belousova, E.D., Frost, M.D., Kuperman, R.A., Bebin, E.M., Korf, B.R., Flamini, J.R., Korman, M.H., Sparagana, S.P., Wu, J.Y., Brehenmacher, T., Stein, K., Berkowitz, N., Bissler, J.J., and Franz, D.N. The effect of everoli-mus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from randomized, placebo-controlled, Phase 3 trial EXIST-1. (2014) Nephrol Dial Transplant 29, 1203-1210.

Funk, J.A., Janech, M.G., Dillion, J.C., Bissler, J.J., Siroky, B.J., and Bell, P.D., Characterization of renal toxicity in mice administered the marine biotoxin domoic Acid. J. Am. Soc. Nephrol. 25, 1187–1197 (2014).

Henske, E. P., Rasooly, R., Siroky, B. & Bissler, J. Tuberous sclerosis complex, mTOR, and the kidney: report of an NIDDK--sponsored workshop. Am. J. Physiol. Renal Physiol. 306, F279–83 (2014).

PresentationsHains. In Defense of the Urinary Tract: Innate Mechanisms for Maintaining Sterility. Pediatric Academic Society/Society of Pediatric Research. Vancouver, Canada.

Hains. Genetic Variations in alpha-Defensin 1-3, Not beta-Defensin Confer UTI Risk in Children with Vesicoureteral Reflux. Pediatric Academic Society/Society of Pediatric Research. Vancouver, Canada.

Hains. Genetic Variations in Vesicoureteral Reflux and its Sequelae. Etteldorf Conference. Memphis, TN.

Hains. Innate Mechanisms for Maintaining Sterility of the Kidney and Urinary Tract. First International UTI Symposia. Lund, Sweden.

Bissler. Improving Experience in Patients with Angiomulipomas Associated with TSC, Madrid, Spain, January 13, 2014.

Bissler. European Association of Urology (EAU), presented findings regarding the safety and efficacy of everolimus for the treatment of renal angiomyolipomata in the context of Tuberous Sclerosis Complex, Stockholm, Sweden, April 14, 2014.

Bissler. Everolimus for Renal Angiomyolipoma Associated with Tuberous Sclerosis Complex: EXIST-2 Long-Term Efficacy and Safety, American Urological Association (AUA), Orlando, FL, May 19, 2014.

Bissler. Management of Renal Angiomyolipoma Associated with TSC, Philadelphia, PA, June 17-18, 2014.

Bissler. TSC Days 2014, Multidisciplinary and Integrated Approach to TSC: A New Era of Personalized Care. Dublin, Ireland September 13-13, 2014.

Bissler. 47th Annual Scientific Meeting of the European Society for Paediatric Nephrology (ESPN), Porto, Portugal, September 18-20, 2014.

Bissler. International TSC/LAM Research Conference. Translation of mTOR Signaling into Targeted Therapy, Beijing, China, October 10-13, 2014.

Wyatt. 51st ERA-EDTA (European Renal Association – European Dialysis and Transplantation Association) Congress, Amsterdam, the Netherlands, June 3, 2014. “IgA nephropathy (anti-Gd1-IgA1, sCD89, sCD71, etc.)”

Wyatt. Grand Rounds, Department of Pediatrics, University of West Virginia, Morgantown, Test Virginia, September 17, 2014, “IgA nephropathy and Henoch Schoenlein purpura”.

Chesney RW: Chair and Speaker, Knockout of the TauT gene pre-disposes C57BL/6 mice to STZ-induced diabetic nephropathy. 19th International Taurine Meeting, Krakow, Poland, 2014.

Chesney RW: Insights into the mechanism of taurinuria related to vitamin D deficiency. 19th International Taurine Meeting, Krakow, Poland, 2014.

Han X, Patters AB, Ito T, Azuma J, Schaffer SW, Chesney RW: Knockout of the Tau T gene predisposes C57 BL/6 mice to a ST2-induced diabetic nephropathy. Joint meeting of the Federation of European Physiological Societies (FEPS) and the Human Physiological Society, Aug. 27-30, 2014, Budapest, Hungary.